U.S. patent application number 11/528757 was filed with the patent office on 2007-04-05 for apparatus for obtaining an image of a blood cell and method for obtaining an image of a blood cell.
This patent application is currently assigned to Sysmex Corporation. Invention is credited to Masanori Nakaya, Ryuichi Tohma.
Application Number | 20070076190 11/528757 |
Document ID | / |
Family ID | 37901562 |
Filed Date | 2007-04-05 |
United States Patent
Application |
20070076190 |
Kind Code |
A1 |
Nakaya; Masanori ; et
al. |
April 5, 2007 |
Apparatus for obtaining an image of a blood cell and method for
obtaining an image of a blood cell
Abstract
A apparatus for obtaining an image of a blood cell is described,
a representative one of which includes image obtainer for obtaining
an image of a predetermined blood cell in a blood sample smeared on
a sample holder; an analysis result obtainer for obtaining an
analysis result of the blood sample; and a controller for
controlling the image obtainer such that the image obtainer obtains
the image under a first imaging condition when the analysis result
does not indicate a presence of a predetermined anomalous cell, and
obtains the image under a second imaging condition to be different
from the first imaging condition when the analysis result indicates
the presence of the predetermined anomalous cell.
Inventors: |
Nakaya; Masanori; (Kobe-shi,
JP) ; Tohma; Ryuichi; (Akashi-shi, JP) |
Correspondence
Address: |
BRINKS HOFER GILSON & LIONE
P.O. BOX 10395
CHICAGO
IL
60610
US
|
Assignee: |
Sysmex Corporation
|
Family ID: |
37901562 |
Appl. No.: |
11/528757 |
Filed: |
September 28, 2006 |
Current U.S.
Class: |
356/39 ;
382/134 |
Current CPC
Class: |
G01N 15/1475 20130101;
G01N 2015/1486 20130101; G01N 15/147 20130101 |
Class at
Publication: |
356/039 ;
382/134 |
International
Class: |
G01N 33/48 20060101
G01N033/48; G06K 9/00 20060101 G06K009/00 |
Foreign Application Data
Date |
Code |
Application Number |
Sep 28, 2005 |
JP |
2005-282291 |
Sep 29, 2005 |
JP |
2005-285067 |
Claims
1. An apparatus for obtaining an image of a blood cell, comprising:
an image obtainer for obtaining an image of a predetermined blood
cell in a blood sample smeared on a sample holder; an analysis
result obtainer for obtaining an analysis result of the blood
sample; and a controller for controlling the image obtainer such
that the image obtainer obtains the image under a first imaging
condition when the analysis result does not indicate a presence of
a predetermined anomalous cell, and obtains the image under a
second imaging condition to be different from the first imaging
condition when the analysis result indicates the presence of the
predetermined anomalous cell.
2. The apparatus according to claim 1, wherein the predetermined
anomalous cell comprises an anomalous nucleated blood cell.
3. The apparatus according to claim 1, further comprising: a
detector for detecting a blood cell comprises a nucleated blood
cell as the predetermined blood cell, wherein the image obtainer
obtains the image of the predetermined blood cell detected by the
detector.
4. The apparatus according to claim 2, wherein the anomalous
nucleated blood cell is selected from the group consisting of an
immature leukocyte, an atypical lymphocytes, a nucleated red blood
cell ,and combinations of thereof.
5. The apparatus according to claim 1, wherein the first imaging
condition relates to a first number of the images, the second
imaging condition relates to a second number of the images, the
second number is larger than the first number.
6. The apparatus according to claim 1 further comprising: a judging
means for judging whether the predetermined blood cell in the image
obtained by the image obtainer is the predetermined anomalous
cell.
7. The apparatus according to claim 6, wherein, under the second
imaging condition, the controller controls the image obtainer such
that the image obtainer stops obtaining a next image, when the
judging means judges that the predetermined blood cell in the image
obtained by the image obtainer is the predetermined anomalous
cell.
8. The apparatus according to claim 7, wherein, under the second
imaging condition, the controller controls the image obtainer such
that the image obtainer stops obtaining a next image, when a
predetermined number of the predetermined blood cells are judged by
the judging means.
9. The apparatus according to claim 8, wherein the first imaging
condition relates to a first number of the images, and the
predetermined number is larger than the first number.
10. The apparatus according to claim 6, wherein the predetermined
anomalous blood cell is selected from the group consisting of an
immature leukocyte, an atypical lymphocyte, a nucleated red blood
cell, and combinations of thereof.
11. The apparatus according to claim 1, wherein the predetermined
anomalous cell comprises aggregated platelets.
12. The apparatus according to claim 11, wherein the first imaging
condition relates to a first position on the sample holder for
obtaining the image, the second imaging condition relates to a
first position on the sample holder for obtaining the image; and
wherein the second position has higher probability of presence of
the aggregated platelets than first position.
13. The apparatus according to claim 12, wherein the first position
is a center or adjacent to the center of the blood sample on the
holder, the second is a margin part of the blood sample on the
holder.
14. The apparatus according to claim 1, wherein the analysis result
obtainer obtains the analysis result from a blood analyzer for
analyzing the presence of the predetermined anomalous cell in the
blood sample.
15. The apparatus according to claim 1, wherein the sample holder
comprises an identification part which identifies the blood sample
and indicates the analysis result of the blood sample.
16. The apparatus according to claim 15, wherein the identification
part comprises a two-dimensional code.
17. A method for obtaining an image of a blood cell comprising:
obtaining a blood analysis result of a blood sample; and obtaining
an imaging of a predetermined anomalous cell in a blood sample
smeared on a sample holder; wherein the image is obtained under a
first imaging condition when the analysis result dose not indicate
a presence of a predetermined anomalous cell, and obtained under a
second imaging condition to be different from a first imaging
condition when the analysis result indicates a presence of a
predetermined anomalous cell.
18. An apparatus for obtaining an image of a blood cell comprising:
an image obtainer for obtaining an image of a predetermined blood
cell in a blood sample smeared on a sample holder; an analysis
result obtainer for obtaining a blood analysis result of the blood
sample; and a controller for controlling the image obtainer such
that the image obtainer obtains a first number of the images when
the analysis result indicates a number of a predetermined blood
cell is larger than a predetermined value, and obtains a second
number of the images, wherein the second number is smaller than the
first number, when the analysis result indicates the number of the
predetermined blood cell is smaller than the predetermined
value.
19. An apparatus for obtaining an image of a blood cell comprising:
a detector for detecting a predetermined blood cell in a blood
sample smeared on a sample holder; an image obtainer for obtaining
a image of the predetermined blood cell detected by the detector;
an analysis result obtainer for obtaining a number of the
predetermined blood cell; and a controller for controlling the
detector such that the detector detects the predetermined blood
cell when the number obtained by the analysis result obtainer is
larger than a predetermined value.
20. The apparatus according to claim 19, wherein the predetermined
blood cell is a red blood cell.
Description
[0001] This application claims priority under 35 U.S.C. .sctn. 119
to Japanese Patent Application Nos. JP2005-282291 filed Sep. 28,
2005 and JP2005-285067 filed Sep. 29, 2005, the entire content of
which is hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to an apparatus for obtaining
an image of a blood cell and a method for obtaining an image of a
blood cell.
BACKGROUND OF THE INVENTION
[0003] Japanese Laid-Open Patent Publication No. 60-162955
discloses an automatic analysis device for blood cells capable of
automatically and simultaneously performing blood cell calculations
and morphological cell classifications from the same sample.
[0004] This automatic cell analysis device is provided with an
automatic cell classifying system for preparing a blood preparation
by smearing a slide glass with blood from a blood sample and
staining the smear then identifying and classifying blood cell
images of a blood preparation, and an automatic cell calculating
system for counting the number of blood cells in a fixed quantity
of the blood cell sample, and the device simultaneously reports the
blood cell calculation and blood cell classification results.
[0005] More specifically, in this blood cell analysis device, a
preparation is enlarged by an optical microscope, a blood cell
image is obtained with a camera, blood cell characteristics are
calculated by a characteristic extraction circuit, and each type of
blood cell is classified. Then, this blood cell analysis device
counts the blood cells based on detection signals for hemoglobin
concentration, white blood cells, red blood cells, and
platelets.
[0006] In this blood cell analyzing device, when the blood cell
count exceeds a normal range set beforehand in a microcomputer, a
signal is sent from the microcomputer to an I/O controller as an
abnormal value of the suspicious sample.
[0007] The I/O controller designates that the blood cell number of
the blood cell classification is two or three times higher for a
confirmed abnormal sample and for an ID preparation matching such a
sample, or changes the blood cell examination method of the
preparation to a method for detailed examination of a specific area
having a high percentage of abnormal cells at an end part of the
smear surface so as to increase abnormal cell detection
sensitivity.
[0008] In this blood cell analyzing device, an abnormal cell is
determined based on the "cell number" calculation information, the
number of cells of the blood cell classification is designated two
or three times higher, or changes the blood cell examination method
for the preparation, however, a problem arises inasmuch as the
abnormal sample determination via the number of blood cells may not
have suitable condition settings for the designated blood cell
numbers and the changed blood cell examination method.
[0009] Specifically, when a sample is determined to be abnormal
based on the blood cell count, a sample which has abnormal blood
cells but the blood cell count is normal can not be determined as
an abnormal sample, such that the conditions can not be suitably
changed.
[0010] Further, when a sample is determined to be abnormal based on
a "blood cell count," a sample that is normal is normal but has a
blood cell count that somewhat exceeds the normal range with the
appearance of abnormal cells may be determined to be an abnormal
sample, such that the condition are unsuitably set.
[0011] That is, the blood cell count is one standard for
determining an abnormal sample (for example, there may be suspicion
of leukemia when the white blood cell count exceeds a normal
number), but the blood cell count is not direct information
indicating the possibility of the occurrence of abnormal cells in a
sample, and is not a reliably standard for determining whether or
not a sample is abnormal.
[0012] That is, even when the white blood cell count is increased
for leukemia, the white blood cell count may be reduced to the
normal range by chemotherapy or the like. In this case, conditions
must be set for blood classification so that an abnormal sample has
abnormal blood cells even when the number of white blood cells is
in the normal range.
[0013] A white cell count that exceeds the normal range may occur
even in healthy people without leukemia depending on their
condition, and it is not desirable that the blood classification
condition settings should unsuitably determine these as abnormal
samples when the condition settings for blood classification might
determine them as normal samples.
[0014] In the above automatic blood cell analyzer, when the number
of blood cells exceeds the normal range, the blood cell count for
blood cell classification is increased two or three fold, to make
the blood cell count less than the normal range and other measures
are not performed.
[0015] However, the following problems arise when the blood cell
number is less than the normal range.
[0016] For example, in an automatic blood cell analyzer, a
predetermined number (for example 100) of white blood cells must be
imaged to classify white blood cells, and if there is a sufficient
abundance of white blood cells in a sample, the white blood cells
for imaging can be easily retrieved and imaged in a short time.
[0017] However, when a predetermined number of white blood cells
must be imaged and there are few white blood cells in a sample, a
long time is required to retrieve the required number of white
blood cells in the sample, thereby lengthening the imaging time.
Moreover, when the required number of white blood cells are not
present in the sample, the imaging process is not completed.
[0018] Additionally, when imaging blood imaging is performed with
auto focusing of the optical microscope using the red blood cell,
which are the most prevalent component in the sample, as a
standard; however, when there are very few red blood cells, such
auto focusing can not be performed.
SUMMARY OF THE INVENTION
[0019] The scope of the present invention is defined solely by the
appended claims, and is not affected to any degree by the
statements within this summary.
[0020] An object of the present invention is to set optimum imaging
conditions to efficiently perform imaging of blood cells based on
blood analysis result.
[0021] The apparatus for obtaining an image of a blood cell of a
first aspect of the present invention includes: (a) ar, image
obtainer for obtaining an image of a predetermined blood cell in a
blood sample smeared on a sample holder; (b) an analysis result
obtainer for obtaining an analysis result of the blood sample; and
(c) a controller for controlling the image obtainer such that the
image obtainer obtains the image under a first imaging condition
when the analysis result does not indicate a presence of a
predetermined anomalous cell, and obtains the image under a second
imaging condition to be different from the first imaging condition
when the analysis result indicates the presence of the
predetermined anomalous cell.
[0022] The method for obtaining an image of a blood cell of a
second aspect of the present invention includes: (a) obtaining a
blood analysis result of a blood sample; and (b) obtaining an
imaging of a predetermined anomalous cell in a blood sample smeared
on a sample holder; wherein the image is obtained under a first
imaging condition when the analysis result dose not indicate a
presence of a predetermined anomalous cell, and obtained under a
second imaging condition to be different from a first imaging
condition when the analysis result indicates a presence of a
predetermined anomalous cell.
[0023] The apparatus for obtaining an image of a blood cell of a
third aspect of the present invention includes: (a) an image
obtainer for obtaining an image of a predetermined blood cell in a
blood sample smeared on a sample holder; (b) an analysis result
obtainer for obtaining a blood analysis result of the blood sample;
and (c) a controller for controlling the image obtainer such that
the image obtainer obtains a first number of the images when the
analysis result indicates a number of a predetermined blood cell is
larger than a predetermined value, and obtains a second number of
the images, wherein the second number is smaller than the first
number, when the analysis result indicates the number of the
predetermined blood cell is smaller than the predetermined
value.
[0024] The apparatus for obtaining an image of a blood cell
includes: (a) a detector for detecting a predetermined blood cell
in a blood sample smeared on a sample holder; (b) an image obtainer
for obtaining a image of the predetermined blood cell detected by
the detector; (c) an analysis result obtainer for obtaining a
number of the predetermined blood cell; and (d) a controller for
controlling the detector such that the detector detects the
predetermined blood cell when the number obtained by the analysis
result obtainer is larger than a predetermined value.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 is a structural view of an examination system that
includes an apparatus for analyzing blood images;
[0026] FIG. 2 is a block diagram of the blood analyzer;
[0027] FIG. 3 is a blood analysis result list related to WBC (white
blood cell: nucleated blood cell);
[0028] FIG. 4 is a blood analysis list related to RBC (red blood
cell);
[0029] FIG. 5 is a blood analysis list related to PLT
(platelet);
[0030] FIG. 6 is a partial enlargement of a sample slide;
[0031] FIG. 7 is a perspective view of a sample slide and
cassette;
[0032] FIG. 8 is a block diagram of an automatic microscope device
and image processing device;
[0033] FIG. 9 is a block diagram of the automatic microscope
controller;
[0034] FIG. 10 is a process flow chart of the automatic microscope
controller;
[0035] FIG. 11 is a process flow chart of the image processing
device;
[0036] FIG. 12 is a process flow chart of the imaging process;
[0037] FIG. 13 is a process flow chart of the white blood cell
mode;
[0038] FIG. 14 is a process flow chart of the platelet mode;
[0039] FIG. 15 is a flow chart showing a modification of the 300
count imaging process;
[0040] FIG. 16 is a process flow chart of the automatic microscope
controller;
[0041] FIG. 17 is a process flow chart of the image processing
device; and
[0042] FIG. 18 is an example of a blood image.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0043] An embodiment of the present invention is described in
detail below with reference to the accompanying drawings.
General System Structure
[0044] In the present embodiment, a blood image analyzer 1, which
images and analyzes blood, is offered as an example of an apparatus
for imaging blood. FIG. 1 shows the general system structure that
includes the blood imaging analyzer 1. This system is installed in
a facility that performs blood examinations, such as a hospital or
the like, and has various types of devices connected thereto via a
network (LAN) 2.
[0045] Devices in this system in addition to the blood image
analyzer 1 include a blood analyzer 3, sample preparation device 4,
handling unit 5, host computer 6, comprehensive review terminal 7
and the like.
Structure of the Blood Analyzer
[0046] The blood analyzer 3 is configured as an automatic blood
cell analyzer that measures predetermined items (multiple items) in
blood and analyzes the results.
[0047] As shown in FIG. 2, the blood analyzer 3 is provided with a
measuring part 31 for performing various measurements by RF/DC
detection, sheath flow DC detection, flow cytometry using a
semiconductor laser, SLS-hemoglobin method or the like, analysis
part 32 for performing analyses based on the measurement results of
the measuring part 31, and a determining part 33 for generating
blood analysis result for predetermined determination items based
on the analysis results.
[0048] The blood analyzer 3 is capable of performing various
measurements related to blood via the measuring part 31.
[0049] Specifically, the measuring part 31 is capable of RBC/PLT
measurements (counted via sheath flow DC detection) for measuring
the number of red blood cells and number of platelets in blood, and
HGB measurement (measured by the SLS-hemoglobin method) for
measuring the amount of hemoglobin in blood, and the analyzing part
32 is capable of calculating the blood cell constants (average red
blood cell volume, average red blood cell hemoglobin, average red
blood cell hemoglobin concentration) based on the RGB, HGB, and HCT
measurement results.
[0050] The measuring part 31 performs 4DIFF measurement (flow
cytometric measurement) for fractionating and measuring groups of
lymphocytes, monocytes, eosinophils, neutrophils, and basophils
among white blood cells as WBC fractionation measurements, WBC/BASO
measurement (flow cytometric measurement) for fractionating and
measuring the number of white blood cells in blood and basophils
among white blood cells, and IMI (immature information) measurement
(RF/DC detection) that is a measurement of immature cell
information.
[0051] The analyzing part 32 generates 4DIFF scattergrams, WBC/BASO
scattergrams, and IMI scattergrams as WBC analyses.
[0052] The 4DIFF scattergram plots the side scattered light
intensity on the X-axis and the side fluorescent light on the
Y-axis via the flow cytometric method, and displays the fraction
groups of red blood cell ghosts, lymphocytes, monocytes,
eosinophils, neutrophils, and basophils.
[0053] The WBC/BASO scattergram plots the side scattered light
intensity on the X-axis and the forward scattered light intensity
on the Y-axis via flow cytometry, and displays the fraction groups
of red blood cell ghosts, basophils among the white blood cells and
other white blood cells (lymphocytes, monocytes, eosinophils,
neutrophils).
[0054] The IMI scattergram shows a two-dimensional distribution of
the size of the blood cells and the internal density of the blood
cells (size of nucleus and the like), and allows for the
discrimination of immature and mature white blood cells.
[0055] The measuring part 31 is capable of performing NRBC
measurement (measurement by flow cytometry) to fractionate and
measure the group of nucleated red blood cells among the blood
cells, and the analyzing part 32 generates an NRBC scattergram as
NRBC analysis.
[0056] The NRBC scattergram plots the side fluorescent light
intensity on the X-axis and the forward fluorescent light on the
Y-axis via the flow cytometric method, and displays the fraction
groups of white blood cells and nucleated red blood cells.
[0057] The measuring part 31 performs RET measurement (measurement
via flow cytometry) to fractionate and measure reticulocytes and
platelets among blood cells, and the analyzing part 32 generates an
RET scattergram as RET analysis.
[0058] The RET scattergram plots the side fluorescent light
intensity on the X-axis and the forward fluorescent light on the
Y-axis via the flow cytometric method, fractionates the mature red
blood cells, reticulocytes, and platelets, and calculates the
reticulocytes percentage, numbers of reticulocytes and red blood
cells, and number of platelets.
[0059] The analyzing part 32 analyzes the RBC particle size
distribution and analyzes the PLT particle size distribution.
[0060] The blood analyzer 3 generates blood analysis result that
includes blood cell number information on nonwhite blood cells, and
abnormal cell information that indicates the possibility of an
occurrence of abnormal cells via the determining part 33 and based
on the previously described measurements and analyses.
[0061] The generated blood analysis result is transmitted together
with the analyzed sample ID (inherent identification information of
the sample) from the blood analyzer 3 to the host computer 7, and
the sample ID and blood analysis result are stored in the memory
part (blood analysis result database) of the host computer.
Blood Analysis Result Generated by the Blood Analyzer
[0062] FIGS. 3 through 5 show lists of blood analysis result. The
blood analysis result relates to the respective blood cells WBC
(white blood cells), RBC (red blood cells), and PLT (platelets),
and provides for each type blood cell a blood cell number
information indicating the number of abnormal cells (mainly blood
cells) ("Abnormal" in the item column in FIGS. 3 through 5), and
abnormal cell information indicating the possibility of the
occurrence of abnormal cells ("Suspect" in the item column in FIGS.
3 through 5).
[0063] The WBC and PLT abnormal cell information of FIG. 3 is
described below after the conditions have been set for the WBC
abnormal cell information (nucleation abnormality information) and
PLT abnormal cell information (platelet clumps information).
Nucleated Blood Cell Information
[0064] The WBC abnormal cell information includes Blast? (blast
cell), Immature Gran? (immature granulocyte), Left shift? (leftward
shift), Atypical Lympho? (atypical lymphocyte), Abn
Lympho/L-Blasts? (atypical lymphocyte and lymphoblast), NRBC?
(nucleated red blood cell), RBC Lyse resistance? (poor hemolysis),
and indicate the possibility of the occurrence of immature
leukocytes that are normally not present in peripheral blood.
[0065] This information includes information indicating the
possibility of the presence of NRBC (nucleated red blood cells; red
blood cells do not normally have a nucleus) as abnormal cell
information related to WBC, and may be called "abnormal nucleated
blood cells" in abbreviation of immature leukocytes (which have a
nucleus), atypical lymphocytes (which have a nucleus), and
nucleated red blood cells.
[0066] Furthermore, the information indicating the possibility of
the occurrence of immature leukocytes is referred to as immature
white blood cell information, the information indicating the
possibility of the occurrence of atypical lymphocytes is referred
to as atypical lymphocyte information, and information indicating
the possibility of the occurrence of nucleated red blood cells is
referred to as nucleated red blood cell information, and these are
all abbreviated as abnormal nucleated blood cell information.
[0067] As shown in FIG. 3, the abnormal nucleated blood cell
information discriminates the possibility of the presence of
abnormal nucleated blood cells by image patterns and the like in
the DIFF scattergram and IMI scattergram; for example, when a
scattergram can not be fractioned, or by dots appearing at a
position at which they do not normally appear in a scattergram.
Platelet Clumps Information
[0068] PLT abnormal cell information (platelet clumps information)
indicates the possibility of the occurrence of platelet clumps that
is not normally generated and includes PLT clumps? (platelet
clumps) and PLT clumps? (platelet clumps. The platelet clumps
information is determined based on scattergrams and the like
similar to abnormal nucleated blood cell information.
Blood Analysis Result Output
[0069] As described above, the generated abnormal nucleated blood
cell information and the blood analysis result (IP message) that
includes platelet clumps information and other information are
transmitted from the blood analyzer 3 together with the analyzed
sample ID (inherent identification information of the sample) to
the host computer, and the sample ID and blood analysis result are
stored in the memory part (blood analysis result database) of the
host computer.
Sample Preparation Device and Handling Unit
[0070] The sample preparation unit 4 automatically prepares a blood
sample preparation from the same sample analyzed by the blood
analyzer 3. The sample preparation device 4 prepares a smear sample
(wedge sample) by smearing a blood sample S on a sample slide 41,
which is a sample carrier, as shown in FIGS. 6 and 7.
[0071] A sample memory part 41a configured by a two-dimensional
code (two-dimensional barcode) is printed in the range of the
sample preparation of the sample carrier (sample slide) 41. The
two-dimensional code 41a includes at least information indicating a
sample ID, and may also include patient name, date of measurement,
and sample blood analysis result analyzed by the blood analyzer
3.
[0072] The sample memory part 41 is mechanically readable by a
device (computer) other than the blood analyzer 3, and information
needed for the sample can be obtained by reading the sample memory
part 41.
[0073] The sample memory part 41 may also be configured by a
unidimensional barcode, or other memory storage medium such as
wireless data.
[0074] Information such as sample ID, patient name, date of
measurement may be printable as humanly readable information 41b on
the sample carrier 41.
[0075] The sample slide 41 with the smeared sample preparation is
housed in the sample cassette 42 in the sample preparation device
4. The sample cassette 42 is transported to the blood image
analyzer 1 by the handling unit 5.
Blood Image Analyzer Structure
[0076] Returning now to FIG. 1, the blood image analyzer 1 is
provided with an automatic microscope device (main imaging device)
110 that has an imaging part for taking a blood image of the blood
sample preparation of the sample, and an image processing device
120 for processing cell identification classifications and the
like, and both devices 110 and 120 are mutually connected so as to
be capable of communicating.
Automatic Microscope Device Structure
[0077] As shown in FIG. 8, the automatic microscope device 110 is
provided with slide glass transporting part 11a for transporting
the sample slide (slide glass) 41 delivered from the handling unit
S within the automatic microscope device 110, and a slide glass
transport drive part 111b for driving the transport part 111a.
[0078] When a cassette 42 is delivered to a predetermined position
by the handling unit 5, the cassette 42 is detected by a cassette
sensor 112a, and the sample slide 41 is removed from the cassette
42. Then, an ID reading part 112b acquires the information such as
sample ID and the like by reading the two-dimensional code of the
sample memory part 41a of the sample slide 41.
[0079] The sample slide 41 is placed on the stage 113a and the
sample arranged on the stage 113a is magnified and observed via a
microscope 114a, the subject blood cells (white blood cells) are
detected by a WBC sensor 114b, and the stage 113a is moved to
change the field of view via a stage drive circuit 113b. Image
focus adjustment is performed by a focus drive circuit 115b based
on an image detected by an auto focus unit 115a. At the same time,
the image is captured by a color CCD camera 116a. An RGB color
image is output from the CCD camera 116a, and image data are
transmitted to the image processing device 120.
[0080] The imaging part of the present invention is configured by
the CCD camera 116a, stage 113a, stage drive circuit 113b, auto
focus unit 115a, and focus drive circuit 115b.
[0081] Various types of controls including the control of the
imaging part in the automatic microscope device 110, and
communication controls for data transmission to the network side
via a network board 117 are accomplished by a automatic microscope
control part 18.
[0082] The automatic microscope control part 118 is provided with a
CPU 118a, ROM 118b, RAM 118c, I/O interface 118d, as shown in FIG.
9. The ROM 118b stores an operating system, control program for
controlling the operation of the automatic microscope device 110,
and data necessary for the execution of the control program. The
CPU 118a can load the control program into the RAM 118c, or can
execute the control program directly from the ROM 118b. Thus, the
data that have been processed by the CPU 118a are sent to the
various parts of the device 110 and devices external to the device
110 (image processing device 120 and the like) via the I/O
interface 118d, and the data needed for processing by the CPU 118a
are received from the various parts of the device 110 or from
devices external to the device 110 (image processing device 120 and
the like via the I/O interface 118d. The CPU 118a controls the
operation of the automatic microscope device 110 by executing the
control program.
Image Processing Device Structure
[0083] Returning now to FIG. 8, the image processing device
(processor) 120 is provided with a CPU 121, ROM 122a, RAM 122b,
display device 123 such as a CRT or the like, input devices such as
a keyboard 124a, special keyboard 124b, mouse 124c and the like,
host I/F 125, network board 126, and hard disk (memory part) 127. A
printer 128 is connected to the image processing device 120.
[0084] In the image processing device 120, the RGB color image
output from the automatic microscope device 110 is subjected to A/D
conversion by an A/D converter 129a, and stored in an image memory
129b. The image stored in the image memory 129b is the object of
processing by the CPU 121.
[0085] The ROM 122a stores an operating system, program for
executing the processing performed by the image processing device
120, and data required for the execution of the program. The CPU
121 can load the program into the RAM 122b, or execute the program
directly from the ROM 122a. Thus, the data that have been processed
by the CPU 121 are sent to devices external to the device 120
(automatic microscope device 110 and the like) via the host I/F 125
or the network board 126, and the data needed for processing by the
CPU 121 are received from the devices external to the device 120
(automatic microscope device 110 and the like) via the host I/F or
network board 126.
[0086] The CPU 121 processes the image data, calculates the
characteristics needed for identification classification of the
blood cells, and identifies and classifies the blood cells based on
these characteristics by executing the program.
[0087] The CPU 121 also displays the identification and
classification results and the blood image on the CRT 123, and
stores the blood image for review on the hard disk 127.
Imaging Process Flow 1
[0088] As shown in FIG. 10, when the sample cassette 42 is detected
by the cassette sensor 112a of the automatic microscope device 110
(step S1-1), the sample slide 41 is removed from the cassette 42
step S1-2), the sample memory part 41a of the sample slide 41 is
read (barcode reading( (step S1-3), and the sample ID
(identification information) is obtained from the sample slide 41.
The obtained sample ID is sent from the automatic microscope device
110 to the image processing device 120 (step S1-4), and the
automatic microscope device 110 awaits reception of the imaging
conditions (step S1-5).
[0089] As shown in FIG. 11, in the image processing device 120,
when the sample ID (identification information) is received from
the automatic microscope device 110 (step S2-1), the memory part
(blood analysis result database) is referenced in the host computer
6 via the network 2, and the blood analysis result corresponding to
the sample ID is obtained (step S2-2; blood analysis result
obtainer).
[0090] Then, a determination is made as to whether or not abnormal
cell information indicating a possibility of the occurrence of
abnormal cells (Suspect Message) is contained in the obtained blood
analysis result (IP message) (step S2-3).
[0091] If abnormal cell information is included in the blood
analysis result, the imaging condition (first imaging condition
relating to the blood cell count number) is set such that the blood
cell count number that indicates the number of imagings for blood
images set at a 100 count, and this imaging condition is sent to
the automatic microscope device 110 (step S2-4).
[0092] When abnormal cell information is included in the blood
analysis result, a determination is made as to whether or not the
abnormal cell information (Suspect Message) relates to WBC (that
is, whether or not abnormal nucleated blood cell information is
included) (step S2-5).
[0093] When abnormal cell information (Suspect Message) related to
WBC is not included, the imaging condition (first imaging condition
related to blood cell count number; normal imaging condition) is
set such that the blood cell count representing the number of blood
cell imagings is set at a 100 count since a possibility of the
presence of abnormal nucleated cells is not included, and the
imaging condition is sent to the automatic microscope device 110
(step S2-4).
[0094] When abnormal cell information (Suspect Message) related to
WBC is included, the imaging condition (second imaging condition
related to blood cell count number; abnormal imaging condition) is
set such that the blood cell count representing the number of blood
cell imagings is set at a 300 count since there is a possibility of
the presence of abnormal nucleated cells, and the imaging condition
is sent to the automatic microscope device 110 (step S2-6).
[0095] Thus, the blood cell count of the imaging condition is set
higher when blood analysis result indicates a possibility of an
occurrence of abnormal nucleated cells than when there is no
indication of a possibility of the occurrence of abnormal nucleated
cells so as to obtain more blood images.
[0096] When abnormal cell information is included in the blood
analysis result, a determination is made as to whether or not the
abnormal cell information (Suspect Message) relates to PLT (that
is, whether or not platelet clumps information is included) (step
S2-7).
[0097] When the abnormal cell information (Suspect Message) does
not include PLT information, the information is not sent to the
automatic microscope device 110, and imaging is performed under an
imaging condition (first imaging position related to the imaging
position) at which imaging is only done at a first position
(initial set position at the center or near center C of the sample
(1/4 the distance of the blood sample S from the edge part); refer
to symbol C in FIG. 7) as a sample imaging position by the
automatic microscope device 110 in a manner described later.
[0098] When the abnormal cell information (Suspect Message) does
include PLT information, a second position (sample edge position;
refer to symbol E in FIG. 7) is set as the sample imaging position
(second imaging condition related to the imaging position) since
platelet clumps has occurred, and this imaging condition is sent to
the automatic microscope device 110 (step S2-8).
[0099] The imaging condition related to the blood cell count number
and the imaging condition related to the imaging position may be
transmitted to the automatic microscope device 110 separately as
described above, or may be sent together.
[0100] Returning now to FIG. 10, when information of the imaging
conditions (imaging condition related to the blood cell count
number and/or imaging condition related to the imaging position) is
received by the automatic microscope controller 117 of the
automatic microscope device 110 (step S1-5), the sample slide 41 is
transported to the stage 113a (step S1-6), and imaging is performed
based on the received imaging conditions (step S1-7).
[0101] White blood cell mode imaging is performed (step S3-1) and
platelet mode imaging (step S3-2) is performed as necessary, as
shown in FIG. 12.
[0102] In the case of white blood cell imaging, the control part
118 discriminates the imaging condition related to the received
blood cell count number (step S3-1-1), and if the imaging condition
is a 100 count (first imaging condition), 100 white blood cell
imagings are performed, whereas if the imaging condition is a 300
count (second imaging condition), 300 white blood cell imagings are
performed, as shown in FIG. 13.
[0103] In the white blood cell mode, imaging is performed at the
first position (initial set position at the center or near center C
of the sample; refer to symbol C in FIG. 7).
[0104] Thus, when the blood analysis result indicates a possibility
of the presence of abnormal nucleated cells, the blood cell count
is increased for imaging such that the abnormal blood cells are
reliably imaged. Moreover, the second imaging condition related to
the blood cell count number is not necessarily a 300 count and may
be any suitable count number.
[0105] In the platelet mode imaging process (step S3-2) that
follows the white blood cell mode imaging process (step S3-1), a
determination is made as to whether or not imaging is necessary
(step S3-2-1). This determination is accomplished by whether or not
an imaging condition related to the imaging position is included in
the received imaging conditions.
[0106] When an imaging condition related to the imaging position is
not included, execution of imaging in the platelet mode is
unnecessary, and the mode ends without imaging being performed.
[0107] When an imaging condition related to the imaging position is
included, the control part 118 controls the imaging part so as to
perform imaging of the sample margin E as the platelet mode imaging
(step S3-2-2). The sample margin E is a position that more readily
has platelet clumps than the sample center C. The control part 118
moves the stage 113a via the stage drive circuit 113b and shifts
the field of view to the margin E so as to image the margin E.
[0108] Thus, when a possibility of the presence of platelet clumps
is indicated, the platelet clumps can be more reliably imaged by
moving the field of view.
Imaging Processing Flow 2
[0109] As shown in FIG. 16, when the sample cassette 42 is detected
by the cassette sensor 112a of the automatic microscope device 110
(step S5-1), the sample slide 41 is removed from the cassette 42
(step S5-2), the sample memory part 41a of the sample slide 41 is
read (barcode reading) (step S5-3), and the sample ID
(identification information) is obtained from the sample slide
41.
[0110] The obtained sample ID is sent from the automatic microscope
device 110 to the image processing device 120 (step S5-4), and the
automatic microscope device 110 awaits reception of the imaging
conditions (step S5-5).
[0111] As shown in FIG. 17, in the image processing device 120,
when the sample ID (identification information) is received from
the automatic microscope device 110 (step S6-1), the memory part
(blood analysis result database) is referenced in the host computer
6 via the network 2, and the blood analysis result corresponding to
the sample ID is obtained (step S6-2; blood analysis result
obtainer).
[0112] Then, the red blood cell number information is referenced in
the obtained blood analysis result, and a determination is made as
to whether or not the red blood cell number indicated in the red
blood cell number information is less than a predetermined value (2
million/.mu.L) (step S6-3). In the present embodiment, the
predetermined value (normal standard for red blood cell number) is
set as the number of red blood cells needed for auto focusing the
automatic microscope device 110.
[0113] If the red blood cell number is less than the predetermined
value, auto focusing of the automatic microscope device 110 is not
performed since accurate imaging cannot be performed, and imaging
termination information is set as the imaging condition information
and sent to the automatic microscope device 110 so as to not
perform wasteful imaging processes (step S-4).
[0114] When the number of red blood cells exceeds a predetermined
value (when imaging), the white blood cell number information is
referenced in the obtained blood cell analysis result and a
determination is made as to whether or not the white blood cell
number indicated in the white blood cell number information is less
than a predetermined value (200 cells/.mu.L). In the present
embodiment, the predetermined value (normal standard of the white
blood cell number) is set at a sufficient white blood cell number
to obtain a blood cell imaging number (blood cell count number)
needed for normal blood cell classification.
[0115] When the white blood cell number exceeds the predetermined
value, the imaging condition (normal imaging condition; first
imaging condition) is set such that the blood cell count number for
indicating the white blood cell number included in the obtained
blood image is set at 100 count, and this imaging condition is sent
to the automatic microscope device 110 (step S6-6).
[0116] When the white blood cell number indicated in the white
blood cell number information is less than the predetermined value,
there are too few white blood cells in the sample and the blood
cell count number is too high when it is the same as the normal
imaging condition such that imaging is impractical in that imaging
requires a long time. At this time the count number is set lower
than the normal imaging condition at a 50 count (normal standard
not met imaging condition; second imaging condition), and this
imaging condition is sent to the automatic microscope device 110
(step S6-7).
[0117] Although the imaging termination information and imaging
condition related to the blood cell count number are sent
separately to the automatic microscope device 110 as described
above, they may also be sent together.
[0118] Returning now to FIG. 16, when the automatic microscope
control part 118 of the automatic microscope device 110 receives
imaging condition information (imaging termination information
and/or imaging information related to blood cell count number)
(step S5-5), a determination is made as to whether or not imaging
termination information is included in the imaging information
(step S5-6).
[0119] When imaging termination information is included, the sample
slide 41 is transported to and stored in the slide storage part
(omitted from the drawing) of the automatic microscope device 110
with being imaged by the imaging part (step S5-7). Thus, samples
that are difficult to image because the red blood cell number is
too low for auto focusing are processed efficiently by not
subjecting the sample to actual imaging and immediately processing
the next sample.
[0120] When imaging termination information is not included,
however, the sample slide 41 is transported to the imaging part
(step S5-8), and imaged under the received imaging condition
related to blood cell count number (step S5-9).
[0121] When imaging, the control part 118 discriminates the
received imaging condition related to the blood cell count number,
and controls the imaging part such that when the imaging condition
is a 100 count (first imaging condition), imaging of white blood
cells is performed 100 times (100 white blood cell images are
taken), whereas when the imaging condition is a 50 count (second
imaging condition), imaging of white blood cells is performed 50
times (50 white blood cell images are taken).
[0122] In the present embodiment, when a plurality of white blood
cells are included in the image obtained by one imaging, only one
white blood cell is extracted for classification, and the blood
cell count number is [1]. In this case, the imaging number equals
the blood cell count number.
[0123] When a plurality of white blood cells are included in the
image obtained by one imaging, a plurality of white blood cells may
be extracted for classification and the blood cell count number may
be more than one. In this case, the imaging number is less than the
blood cell count number, and the blood cell count number is
obtained efficiently with fewer imagings.
[0124] Thus, when imaging using the second imaging condition in the
present embodiment, it is possible to avoid the situation of taking
a longer time for imaging more white blood cells when there are
fewer white blood cells because fewer imagings are needed than
under the first imaging condition.
[0125] FIG. 18 shows an example of an obtained image with a single
white blood cell W near the center of the image. A plurality of red
blood cells R are present around the white blood cell. Auto
focusing is accomplished based on the red blood cells present
around the white blood cell.
Blood Cell Classification Process
[0126] The obtained blood cell image (sample image; white blood
cell digital image) is sent to the image processing device 120, and
the image processing device performs blood cell (white blood cell)
characteristic extraction processing and blood cell (white blood
cell) classification processing based on the sample image.
[0127] The characteristics extraction process is performed by
separating pixels equivalent to the nucleus and pixels equivalent
to the cytoplasm in the sample image of the white blood cell from
other pixels.
[0128] The classification process identifies the types of object
blood cells using feature parameters related to the nucleus and
feature parameters related to cytoplasm, and classifies the blood
cells of the blood cell count number.
[0129] The white blood cell (nucleated blood cell) classification
process classifies the object blood cells as six types of mature
white blood cells (stab neutrophil, segmented neutrophil,
eosinophil, basophil, lymphocyte, monocyte) and erythroblasts. The
six types of mature white blood cells are normal nucleated blood
cells, and three types of immature leukocytes, and erythroblasts
are abnormal nucleated blood cells.
[0130] When the blood analysis result of the blood analyzer 3
indicates a possibility of the presence of abnormal nucleated blood
cells as described above, the blood cell count number is increased
and the number of classification object blood cells is increased to
allow accurate detection and classification of the abnormal
nucleated blood cells.
[0131] Furthermore, when the blood analysis result of the blood
analyzer 3 indicates the possibility of the presence of platelet
clumps, the platelet clumps can be handled to avoid reporting a low
platelet value due to the agglutination by imaging the sample
margin part in which platelet clumps is easily discovered.
[0132] The obtained image and classification result are sent
together with the sample ID from the blood image analyzer 1 to the
host computer 6, and are stored in the host computer 6. The blood
analysis result, obtained images, and blood cell classification
results stored in the host computer 6 can be viewed on the
comprehensive review terminal 7.
[0133] FIG. 15 shows a modification of the 300 count imaging
process (imaging process under the second imaging condition related
to blood cell count number; step S3-1-3) of FIG. 13.
[0134] When the received imaging condition related to the blood
cell count number is the second imaging condition (300 count), the
automatic microscope control part 118 first performs imaging under
the first imaging condition (100 count) related to the blood cell
count number (step S401).
[0135] The count number is set at 100 (blood cell count number of
the first imaging condition (step S4-2), the sample is the
information is sent to the image processing device 120, and the
count is increased 1 (step S4-3).
[0136] In the image processing device 120, the sample image is
received and stored in a memory such as a RAM or the like (step
S4-4), and the blood cell (white blood cell) classification process
is performed based on the sample image. The classification result
is stored in memory (step S4-6) and sent to the automatic
microscope device 110 side (step S4-7).
[0137] When the imaged blood cell classification result is received
(step S4-8), the automatic microscope control part 118 determines
whether or not the classification result is an abnormal nucleated
blood cell.
[0138] When the imaged blood cell is an abnormal nucleated blood
cell, further imaging is suspended and the imaging under the second
imaging condition related to blood cell count number ends.
[0139] When the imaged blood cell is not an abnormal nucleated
blood cell, the process returns to step S4-4 and imaging is
repeated until the count value attains the blood cell count value
of the second imaging condition (300 count).
[0140] According to this process, since imaging is performs until
at least one abnormal nucleated blood cell is included in the
classification result during imaging under the second imaging
condition related to blood count number, it is possible to reliably
image an abnormal nucleated blood cell with relatively few
imagings. Moreover, when imaging under the second imaging
condition, the number of imagings equal to the imagings under the
first imaging condition (first blood count number=100) is ensured,
and a number of sample images required for classification is also
ensured.
[0141] When imaging under the second imaging condition, a maximum
value of the blood count number is set (second blood count
number=100), and imaging is stopped when the imaging number attains
the maximum value even if an abnormal nucleated cell is not
included in the classification result, thus preventing unending
imaging.
[0142] The present invention is not limited to the previously
described embodiment.
[0143] For example, conditions related to whether or not to image
may be added to the imaging conditions related to blood cell count
number and imaging conditions related to imaging position. Such a
condition related to whether or not to image may to add a condition
stipulating that imaging is unnecessary due to a high degree of
abnormality when information indicating a high degree of
abnormality such as blasts? (blast cells) are included as WBC
abnormal cell information (Suspect Message) so as to perform human
microscopic observation without imaging by the blood image analyzer
1.
[0144] Conversely, a condition may be added that stipulates imaging
is unnecessary when the blood analysis result lacks any indication
of the possibility of a presence of abnormal cell information,
since the need for analysis is low due to the low degree of
abnormality.
[0145] Such conditions related to whether or not imaging is needed
can be determined prior to the processing of steps S3-1-1 of FIG.
13.
[0146] Although the blood imaging device 1 obtains sample blood
analysis result from a host computer in the above embodiment, such
information may also be obtained from the blood analyzer 3.
Furthermore, when the sample memory part (two-dimensional code) 41a
of the sample slide 41 stores blood analysis result, such
information may also be obtained from the sample memory part
41a.
[0147] In the above embodiment, when abnormal cell information
(Suspect Message) is included in the WBC, the possibility of a
presence of abnormal nucleated cells is indicated, and the second
imaging condition is set to set the blood cell count number
indicating the number of blood cell images to be taken at a 300
count. However, a second imaging condition may differ and be set in
accordance with the types of abnormal cell information present in
plurality. For example, when the suspect Message is Blasts?, the
blood cell count number may be set at a 200 count, and when the
Suspect Message is Immature Gran?, the blood cell count may be set
at a 400 count.
[0148] The blood analysis result that includes the white blood cell
number information, red blood cell number information also may be
obtained by the blood image analyzer 1 itself. For example, a
sample may be imaged by the imaging part of the blood image
analyzer 1 at a relatively wide field of view to generate blood
analysis result that includes the white blood cell number
(distribution density of the white blood cells) and red blood cell
number (distribution density of the red blood cells) in the sample,
and the imaging conditions may then be set based on the generated
blood analysis result.
* * * * *